Non-Ketotic Hyperglycinemia

Non-ketotic hyperglycinemia (NKH), or glycine encephalopathy, is a rare, autosomal recessive disease characterised by accumulation of glycine in body fluids and tissues. The disease typically becomes apparent soon after birth with progressive lethargy and severe neurological symptoms, including intractable seizures, developmental delay and psychomotor retardation. Current treatments not effective long-term and are not curative.

NKH is caused by mutations in genes (GLDC or AMT) encoding the glycine cleavage system (GCS), a component of mitochondrial folate metabolism. Current projects make use of a novel mouse model, in which reduced expression of the NKH-causing gene Gldc (encoding glycine decarboxylase) causes loss of GCS activity and features of NKH including elevated glycine in urine and plasma, hydrocephalus and early lethality (Pai 2015).

A proportion of GCS-deficient mice (lacking Amt or Gldc) also develop NTDs, confirming the involvement of this enzyme system in defects of pre-natal and post-natal development of the central nervous system (Narisawa 2012).

Our research aims to better understand the disease process and to develop novel therapies. Current projects include: